Chemopreventive strategies and prognostication for gastric cancer

Abstract

Gastric cancer is the fourth frequent cause of cancer death worldwide, the challenge of reducing gastric cancer-related mortality continues. This series of studies addresses some clinical questions related to gastric cancer, including chemopreventive strategies (anti-hypertensive drugs, non-aspirin non-steroidal anti-inflammatory drugs [NSAIDs], and aspirin) and some issues related to surgical treatment. Anti-hypertensive drugs are the most frequently prescribed therapeutic drugs that require long-term use. Their effects on gastric cancer development are still not well studied. A total of 17,622 H. pylori-eradicated subjects with hypertension were analyzed. We found that calcium channel blockers treatment was associated with reduced gastric cancer development in duration- and dose-response manner. At the same time, none of the other types of anti-hypertensive drugs (angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers, and diuretics) were associated with developing gastric cancer. We investigated the association between non-aspirin NSAIDs and gastric cancer risk. A total of 92,017 H. pylori-eradicated subjects were enrolled. Non-aspirin NSAIDs were not associated with a reduced risk of gastric cancer among H. pylori-eradicated patients. This result contradicts previous meta-analyses that found NSAIDs (both aspirin and non-aspirin NSAIDs) beneficial in gastric cancer development. Aspirin for chemoprevention has not been widely advocated as there is a concern of bleeding side effects. We enrolled a cohort of 87,967 H. pylori–eradicated subjects with a median follow-up of 10.3 years. We found that low-dose aspirin was associated with a 25% and 49% lower risk of gastrointestinal cancer and its associated mortality, respectively. However, aspirin was associated with a 50% higher bleeding risk and 52% higher bleeding-related mortality. Treating H. pylori before aspirin initiation with concomitant PPI use could maximize the benefit-risk ratio of aspirin. The extracapsular extension (ECE) of lymph nodes or not is one of the histological characteristics that may influence the prognosis of gastric cancer. We validated the detrimental prognostic role of ECE among lymph node-positive gastric cancer patients. Besides, the current ECE grading system (initially used for squamous cell carcinoma in head and neck cancers) is not suitable for gastric cancer. Evidence supporting laparoscopic technique in gastrectomy for gastric cancer from countries/regions with relatively lower patient volumes is still lacking. We found that laparoscopic gastrectomy is comparable to open surgery for gastric cancer, even in advanced tumors in our center. The findings of this study may contribute to the existing evidence supporting the general use of laparoscopic gastrectomy for gastric cancer outside of high-volume centers. We also studied changes in characteristics, treatment, and survival in patients with adenocarcinoma of the esophagogastric junction (AEJ) over 36 years at a single tertiary referral center. We found that the survival of AEJ patients under surgical resection has improved over the last four decades. Appropriate patient selection is the most important reason for such a better outcome. Gastric cancer-related mortality can be reduced by comprehensively adopting proper chemopreventive strategies and refining current treatments.